Skip to main content

Advertisement

SpringerLink
Log in

Transcriptomic and histological analysis of exposed facial skin areas wrinkled or not and unexposed skin

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Background

Skin aging involves genetic, environmental and hormonal factors. Facial wrinkles also depend on muscular activity. Gene expression investigation may be useful for new anti-aging products.

Methods and Results

To evaluate structure and gene expression differences among exposed and unexposed skin in menopausal women. Cross-sectional study, including 15 menopausal women, 55–65 years, phototype III; photo-exposed, periorbital wrinkles (A1), preauricular, not wrinkled (A2), and unexposed gluteal (A3) areas were described and compared by non-invasive measures, histology, immunohistochemistry and gene expression (RNASeq); participants mean age was 61yo, presenting moderate periorbital wrinkles and light facial photodamage. Higher roughness, wrinkles number and echogenicity were observed in A1 and A2 versus A3. Decreased epidermal thickness and dermal collagen IV were demonstrated in A1 versus A2 and A3. Exposed areas impacted different pathways compared to unexposed. Exposed wrinkled skin (A1) showed impact on cell movement with decreased inflammatory activation state. Pathways related to lipid and aminoacids metabolism were modulated in non-wrinkled exposed (A2) compared to unexposed (A3) skin.

Conclusions

Expected histological findings and gene expression differences among areas were observed. Photoaging in menopausal women may modulate lipid and aminoacids metabolism and decrease inflammatory and keratinization pathways, cellular homeostasis, immune response, fibrogenesis and filament formation. These findings may help development of new therapies for skin health and aging control.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Babamiri K, Nassab R (2010) Cosmeceuticals: the evidence behind the retinoids. Aesthet Surg J 30:74–77. https://doi.org/10.1177/1090820X09360704

    Article  PubMed  Google Scholar 

  2. Bens G (2014) Sunscreens. Adv Exp Med Biol 810:429–463. https://doi.org/10.1007/978-1-4939-0437-2_25

    Article  PubMed  Google Scholar 

  3. Birch-Machin MA, Russell EV, Latimer JA (2013) Mitochondrial DNA damage as a biomarker for ultraviolet radiation exposure and oxidative stress. Br J Dermatol 169(Suppl 2):9–14. https://doi.org/10.1111/bjd.12207

    Article  CAS  PubMed  Google Scholar 

  4. Brandt FS, Cazzaniga A, Hann M (2011) Cosmeceuticals: current trends and market analysis. Semin Cutan Med Surg 30:141–143. https://doi.org/10.1016/j.sder.2011.05.006

    Article  CAS  PubMed  Google Scholar 

  5. Caetano LVN, Soares JLM, Bagatin E, Miot HA (2016) Reliable assessment of forearm photoageing by high-frequency ultrasound: a cross-sectional study. Int J Cosmet Sci 38(2):170–177. https://doi.org/10.1111/ics.12272

    Article  Google Scholar 

  6. Calleja-Agius J, Muscat-Baron Y, Brincat MP (2007) Skin ageing. Menopause Int 13:60–64. https://doi.org/10.1258/175404507780796325

    Article  CAS  PubMed  Google Scholar 

  7. Cao C, Xiao Z, Wu Y, Ge C (2020) Diet and skin aging-from the perspective of food nutrition. Nutrients 12:870. https://doi.org/10.3390/nu12030870

    Article  CAS  PubMed Central  Google Scholar 

  8. Carruthers A, Carruthers J, Hardas B, Kaur M, Goertelmeyer R, Jones D, Rzany B, Cohen J, Kerscher M, Flynn TC, Maas C, Sattler G, Gebauer A, Pooth R, McClure K, Simone-Korbel U, Buchner L (2008) A validated grading scale for crow’s feet. Dermatol Surg 34(Suppl 2):S173–S178. https://doi.org/10.1111/j.1524-4725.2008.34367.x

    Article  CAS  PubMed  Google Scholar 

  9. Carvalho PRS, Sumita JM, Soares JLM, Sanudo A, Bagatin E (2017) Forearm skin aging: characterization by instrumental measurements. Int J Cosmet Sci 39:564–571. https://doi.org/10.1111/ics.12407

    Article  CAS  PubMed  Google Scholar 

  10. Cho S, Shin MH, Kim YK, Seo JE, Lee YM, Park CH, Chung JH (2009) Effects of infrared radiation and heat on human skin aging in vivo. J Investig Dermatol Symp Proc 14:15–19. https://doi.org/10.1038/jidsymp.2009.7

    Article  CAS  PubMed  Google Scholar 

  11. Cho BA, Yoo SK, Seo JS (2018) Signatures of photo-aging and intrinsic aging in skin were revealed by transcriptome network analysis. Aging 10:1609–1626. https://doi.org/10.18632/aging.101496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Choi EH (2019) Aging of the skin barrier. Clin Dermatol 37:336–345. https://doi.org/10.1016/j.clindermatol.2019.04.009

    Article  PubMed  Google Scholar 

  13. de Diego I, Peleg S, Fuchs B (2019) The role of lipids in aging-related metabolic changes. Chem Phys Lipids 222:59–69. https://doi.org/10.1016/j.chemphyslip.2019.05.005

    Article  CAS  PubMed  Google Scholar 

  14. Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR (2013) STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29:15–21. https://doi.org/10.1093/bioinformatics/bts635

    Article  CAS  PubMed  Google Scholar 

  15. Draelos ZD (2009) Cosmeceuticals: undefined, unclassified, and unregulated. Clin Dermatol 27:431–434. https://doi.org/10.1016/j.clindermatol.2009.05.005

    Article  PubMed  Google Scholar 

  16. Draelos ZD (2011) The art and science of new advances in cosmeceuticals. Clin Plast Surg 38(3):397–407. https://doi.org/10.1016/j.cps.2011.02.002

    Article  PubMed  Google Scholar 

  17. Elewa RM, Abdallah MA, Zouboulis CC (2015) Age-associated skin changes in innate immunity markers reflect a complex interaction between aging mechanisms in the sebaceous gland. J Dermatol 42:467–476. https://doi.org/10.1111/1346-8138.12793

    Article  CAS  PubMed  Google Scholar 

  18. Fitzpatrick TB (1988) The validity and practicality of sun-reactive skin types I through VI. Arch Dermatol 124:869–871. https://doi.org/10.1001/archderm.124.6.869

    Article  CAS  PubMed  Google Scholar 

  19. Flament F, Bazin R, Laquieze S, Rubert V, Simonpietri E, Piot B (2013) Effect of the sun on visible clinical signs of aging in Caucasian skin. Clin Cosmet Investig Dermatol 6:221–232. https://doi.org/10.2147/CCID.S44686

    Article  PubMed  PubMed Central  Google Scholar 

  20. Franca K, Cohen JL, Grunebaum L (2013) Cosmeceuticals for recurrence prevention after prior skin cancer: an overview. J Drugs Dermatol 12:516–518

    CAS  PubMed  Google Scholar 

  21. GTEx (Consortium 2015) Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science 348(6235):648–660. https://doi.org/10.1126/science.1262110

  22. Hausmann C, Zoschke C, Wolff C, Darvin ME, Sochorova M, Kovacik A, Wanjiku B, Schumacher F, Tigges J, Kleuser B, Lademann J, Fritsche E, Vavrova K, Ma N, Schafer-Korting M (2019) Fibroblast origin shapes tissue homeostasis, epidermal differentiation, and drug uptake. Sci Rep 9:2913. https://doi.org/10.1038/s41598-019-39770-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hughes MC, Williams GM, Baker P, Green AC (2013) Sunscreen and prevention of skin aging: a randomized trial. Ann Intern Med 158:781–790. https://doi.org/10.7326/0003-4819-158-11-201306040-00002

    Article  PubMed  Google Scholar 

  24. Iqbal B, Ali J, Baboota S (2018) Recent advances and development in epidermal and dermal drug deposition enhancement technology. Int J Dermatol 57:646–660. https://doi.org/10.1111/ijd.13902

    Article  PubMed  Google Scholar 

  25. Jonca N (2019) Ceramides metabolism and impaired epidermal barrier in cutaneous diseases and skin aging: focus on the role of the enzyme PNPLA1 in the synthesis of ω-O-acylceramides and its pathophysiological involvement in some forms of congenital ichthyoses. OCL 26:17. https://doi.org/10.1051/ocl/2019013

    Article  Google Scholar 

  26. Kim EJ, Jin XJ, Kim YK, Oh IK, Kim JE, Park CH, Chung JH (2010) UV decreases the synthesis of free fatty acids and triglycerides in the epidermis of human skin in vivo, contributing to development of skin photoaging. J Dermatol Sci 57:19–26. https://doi.org/10.1016/j.jdermsci.2009.10.008

    Article  CAS  PubMed  Google Scholar 

  27. Kimball AB, Alora-Palli MB, Tamura M, Mullins LA, Soh C, Binder RL, Houston NA, Conley ED, Tung JY, Annunziata NE, Bascom CC, Isfort RJ, Jarrold BB, Kainkaryam R, Rocchetta HL, Swift DD, Tiesman JP, Toyama K, Xu J, Yan X, Osborne R (2018) Age-induced and photoinduced changes in gene expression profiles in facial skin of Caucasian females across 6 decades of age. J Am Acad Dermatol 78(29–39):e7. https://doi.org/10.1016/j.jaad.2017.09.012

    Article  CAS  Google Scholar 

  28. Kohl E, Steinbauer J, Landthaler M, Szeimies RM (2011) Skin ageing. J Eur Acad Dermatol Venereol 25:873–884. https://doi.org/10.1111/j.1468-3083.2010.03963.x

    Article  CAS  PubMed  Google Scholar 

  29. Kolovou GD, Bilianou HG (2008) Influence of aging and menopause on lipids and lipoproteins in women. Angiology 59:54S-S57. https://doi.org/10.1177/0003319708319645

    Article  PubMed  Google Scholar 

  30. Lee YM, Kim YK, Chung JH (2009) Increased expression of TRPV1 channel in intrinsically aged and photoaged human skin in vivo. Exp Dermatol 18:431–436. https://doi.org/10.1111/j.1600-0625.2008.00806.x

    Article  CAS  PubMed  Google Scholar 

  31. Lighthall JG (2018) Rejuvenation of the upper face and brow: neuromodulators and fillers. Facial Plast Surg 34:119–127. https://doi.org/10.1055/s-0038-1637004

    Article  CAS  PubMed  Google Scholar 

  32. Mercurio DG, Jdid R, Morizot F, Masson P, Maia Campos PM (2016) Morphological, structural and biophysical properties of French and Brazilian photoaged skin. Br J Dermatol 174:553–561. https://doi.org/10.1111/bjd.14280

    Article  CAS  PubMed  Google Scholar 

  33. Newburger AE (2009) Cosmeceuticals: myths and misconceptions. Clin Dermatol 27:446–452. https://doi.org/10.1016/j.clindermatol.2009.05.008

    Article  PubMed  Google Scholar 

  34. Nguyen TT, Gobinet C, Feru J, Brassart-Pasco S, Manfait M, Piot O (2012) Characterization of type I and IV collagens by raman microspectroscopy: identification of spectral markers of the dermo-epidermal junction. Spectroscopy 27(5–6):421–7. https://doi.org/10.1155/2012/686183

    Article  CAS  Google Scholar 

  35. Nkengne A, Bertin C (2013) Aging and facial changes–documenting clinical signs, part 1: clinical changes of the aging face. Skinmed 11:281–286

    PubMed  Google Scholar 

  36. Oyewole AO, Birch-Machin MA (2015) Sebum, inflammasomes and the skin: current concepts and future perspective. Exp Dermatol 24:651–654. https://doi.org/10.1111/exd.12774

    Article  CAS  PubMed  Google Scholar 

  37. Palmer DM, Kitchin JS (2010) Oxidative damage, skin aging, antioxidants and a novel antioxidant rating system. J Drugs Dermatol 9:11–15

    PubMed  Google Scholar 

  38. Papsdorf K, Brunet A (2019) Linking lipid metabolism to chromatin regulation in aging. Trends Cell Biol 29:97–116. https://doi.org/10.1016/j.tcb.2018.09.004

    Article  CAS  PubMed  Google Scholar 

  39. Rahimpour Y, Hamishehkar H (2012) Liposomes in cosmeceutics. Expert Opin Drug Deliv 9:443–455. https://doi.org/10.1517/17425247.2012.666968

    Article  CAS  PubMed  Google Scholar 

  40. Rinnerthaler M, Bischof J, Streubel MK, Trost A, Richter K (2015) Oxidative stress in aging human skin. Biomolecules 5:545–589. https://doi.org/10.3390/biom5020545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Rogers J, Harding C, Mayo A, Banks J, Rawlings A (1996) Stratum corneum lipids: the effect of ageing and the seasons. Arch Dermatol Res 288:765–770. https://doi.org/10.1007/BF02505294

    Article  CAS  PubMed  Google Scholar 

  42. Shanbhag S, Nayak A, Narayan R, Nayak UY (2019) Anti-aging and sunscreens: paradigm shift in cosmetics. Adv Pharm Bull 9:348–359. https://doi.org/10.15171/apb.2019.042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Shen Y, Kim AL, Du R, Liu L (2016) Transcriptome analysis identifies the dysregulation of ultraviolet target genes in human skin cancers. PLoS ONE 11:e0163054. https://doi.org/10.1371/journal.pone.0163054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Waldera Lupa DM, Kalfalah F, Safferling K, Boukamp P, Poschmann G, Volpi E, Gotz-Rosch C, Bernerd F, Haag L, Huebenthal U, Fritsche E, Boege F, Grabe N, Tigges J, Stuhler K, Krutmann J (2015) Characterization of Skin Aging-Associated Secreted Proteins (SAASP) produced by dermal fibroblasts isolated from intrinsically aged human skin. J Invest Dermatol 135:1954–1968. https://doi.org/10.1038/jid.2015.120

    Article  CAS  PubMed  Google Scholar 

  45. Wolf DE, Samarasekera C, Swedlow JR (2007) Quantitative analysis of digital microscope images. Methods Cell Biol 81:365–396. https://doi.org/10.1016/S0091-679X(06)81017-4

    Article  PubMed  Google Scholar 

  46. Zasada M, Budzisz E (2019) Retinoids: active molecules influencing skin structure formation in cosmetic and dermatological treatments. Postepy Dermatol Alergol 36:392–397. https://doi.org/10.5114/ada.2019.87443

    Article  PubMed  PubMed Central  Google Scholar 

  47. Zhang S, Duan E (2018) Fighting against skin aging: the way from bench to bedside. Cell Transplant 27:729–738. https://doi.org/10.1177/0963689717725755

    Article  PubMed  PubMed Central  Google Scholar 

  48. Zhuang Y, Lyga J (2014) Inflammaging in skin and other tissues—the roles of complement system and macrophage. Inflamm Allergy Drug Targets 13:153–161. https://doi.org/10.2174/1871528113666140522112003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Dr. Gopi Menon for his comments on the histology analysis of tissues relevant for this work.

Funding

This study was funded by Avon Products Inc (NY, NY, 10901 Suffern, USA), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES—Finance Code 001); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP 2014/27198-8).

Author information

Author notes

  1. Renan Paulo Martin and Patricia Varela have contributed equally to this work

Authors and Affiliations

  1. McKusick-Nathans Department of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA

    Renan Paulo Martin

  2. Department of Biophysics, Universidade Federal de Sao Paulo, São Paulo, Brazil

    Patricia Varela, Caio Peres Gomes, Maryana Mara Marins, Rafael Filippelli-Silva & João Bosco Pesquero

  3. Department of Dermatology, Universidade Federal de Sao Paulo, São Paulo, Brazil

    Samira Yarak, Juliana L. M. Soares & Edileia Bagatin

  4. Department of Preventive Medicine, Universidade Federal de Sao Paulo, São Paulo, Brazil

    Adriana Sanudo

  5. Avon Products Inc., Suffern, New York, NY, 10901, USA

    Jolanta Idkowiak-Baldys, Siming Chen, Cheng Hwang, Yong Zhuang & John Lyga

Authors
  1. Renan Paulo Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patricia Varela
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Caio Peres Gomes
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maryana Mara Marins
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rafael Filippelli-Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Samira Yarak
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Juliana L. M. Soares
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Adriana Sanudo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jolanta Idkowiak-Baldys
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Siming Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Cheng Hwang
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yong Zhuang
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. John Lyga
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. João Bosco Pesquero
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Edileia Bagatin
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

RPM, PV, and RFS analyze RNA-Seq data; RPM and PV drafted the manuscript; CPG and MMM conduced validation analysis experiments; SY and JLMS performed histological and immunohistochemistry experiments; JIB, SC, CH, and YZ, analyze histological and genetics data; AS perform statistical analysis; JL, JBP, and EB designed and supervised the research; All authors revised and approved the final manuscript.

Corresponding authors

Correspondence to João Bosco Pesquero or Edileia Bagatin.

Ethics declarations

Conflict of interest

RPM, PV, CPG, MMM, RFS, AS, SY, JLMS, JBP, and EB declare no conflict of interest. JIB, SC, CH, YZ, and JL work for Avon Products Inc (NY, NY, 10901 Suffern, USA). The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Ethical approval

All procedures performed in this study which involves human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (XLSX 356 kb)

Supplementary file2 (XLSX 22 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Martin, R.P., Varela, P., Gomes, C.P. et al. Transcriptomic and histological analysis of exposed facial skin areas wrinkled or not and unexposed skin. Mol Biol Rep 49, 1669–1678 (2022). https://doi.org/10.1007/s11033-021-06973-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-021-06973-y

Keywords

Search

Navigation